The overall objective of this proposal is to determine the impact of the new Haemophilus conjugate vaccines on Haemophilus influenzae type b disease in Minnesota and in Dallas County, Texas. One of the new conjugate Haemophilus vaccines currently licensed for use in U.S. children greater than or equal to 18 months of age provided significant protection against Haemophilus disease in Finnish infants, but not in native Alaskan infants. These results suggest that host or environmental factors affect the efficacy of Haemophilus vaccines. In Minnesota and Dallas County there are regional differences in : 1) the age-specific incidence of Haemophilus disease; 2) the protective efficacy achieved in children vaccinated with the first generation Haemophilus type b polysaccharide vaccines; and 3) the risk of primary Hib disease in children attending day care. These differences provide a unique opportunity to further our understanding of factors that affect the epidemiology of Haemophilus disease. In Aim 1, we will perform a case-control study to measure the protective efficacy of the new Haemophilus conjugate vaccines as they are introduced in the study areas. We will monitor the impact of these vaccines on the incidence of Haemophilus disease through active disease surveillance that achieves a high degree of case ascertainment. In Aim 2, we will complete case-control studies determining the risk of primary haemophilus disease in children attending day care facilities, and we will assess the contribution of certain day care characteristics and practices to the risk of disease. In Aim 3, we will investigate the immune responses of infants 2 and 12 months of age vaccinated with the new conjugate Haemophilus vaccines, comparing the responses of infants by type of conjugate vaccine, age at vaccination and geographic area. Immune responses will be determined by several methods including total and isotype-specific antibody responses, complement mediated bactericidal activity and opsonic activity. The result of these studies will allow us to assess the effectiveness of the conjugate vaccines in preventing disease in our study areas. They also may permit us to describe immunologic factors responsible for differences in protective efficacy observed with Haemophilus vaccines.